This project will investigate the nature of cellular events involved in the induction and production of interferon in leukocyte cultures. We have already demonstrated that the population of interferon producting leukocytes is different from the population of lymphocytes which synthesize DNA in response to mitogenic stimulation. This was demonstrated by separating the cells on an albumin gradient. We will continue to employ this technique for separating cells. This project will study whether macrophages have differential effects on blastogenesis and interferon production, the relationship of increased rates of RNA and protein synthesis to blastogenesis and/or interferon production, and the nature of the cells involved in the induction and production of interferon. Cells will be obtained from human tonsil and from mouse spleen. Several mitogens will be employed in this study, including phytohemagglutinin, tuberculin, staphyloccal antigen, and pokeweed mitogen. Induced increments of DNA, RNA and protein synthesis in different fractions of lymphoid cells will be measured by the incorporation of isotopically labeled precursor. Interferon will be assayed by reduction of plaques of vesicular stomatitis virus on appropriate cell lines. Lymphoid cells will be separated on an albumin gradient. Antisera such as anti-theta, anti-immunoglobulin, and anti-MBLA will also be used to eliminate certain populations of cells. Populations of cells thus partially purified will be assayed for their functions as a separate population. In addition, populations will be mixed in various combinations to define the cellular interaction which is requisite for mitogen-induced interferon production.